Abstract

The kinetics of the sorption of a number of solutes by theplastics of intravenous delivery systems were investigated.Models based on diffusion theory and compartmental analysiswere developed and examined for .their ability to describethe uptake of a number of solutes from aqueous solutionsstored in contact with the plastics. In deriving diffusionequations it has been assumed, firstly, that diffusion ofsolute in the plastic matrix is the rate-limiting step inthe sorption process (matrix-controlled sorption) and,secondly, that both the plastic matrix and an interfacialresistance barrier contribute to the diffusional resistanceencountered by the solute molecule (intermediate diffusionkinetics). The situation in which diffusion across theinterfacial resistance barrier is the rate-limiting stepwas also considered.The ability of the diffusion and compartment models todescribe and predict the sorption of the nonelectrolytes,nitroglycerin and diazepam, was examined. The diffusionmodel seemed to be the more satisfactory model in respectof both description and prediction of the drug uptake. Thecompartment model appeared to describe the drug uptake atearlier times, but was not able to describe the loss asequilibrium was approached; nor could that model beemployed as a predictive method. The complete time-course,including equilibrium, of the sorption of nitroglycerin anddiazepam was well-described by the (matrix-control) diffusion model. The diffusion model was also found topredict accurately the rate and extent of nitroglycerin anddiazepam loss from solutions stored in plastic infusionbags of different sizes and containing various volumes ofsolution.The sorption of several weak electrolytes, specifically pnitrophenol,p-toluidine, warfarin sodium andtrifluoperazine dihydrochloride, during storage ofsolutions of various pH in plastic infusion bags was alsostudied. The rate and extent of sorption varied with pH ina manner suggesting preferential uptake of the unionisedspecies. It was assumed that only the unionised specieswas sorbed by the plastic matrix and the diffusion modelwas modified accordingly. The uptake of p-nitrophenol andp-toluidine was adequately described by the matrix-controldiffusion model, confirming quantitatively the relationshipbetween solute uptake and fraction unionised. However, theuptake of warfarin sodium and trifluoperazinedihydrochloride was significantly better described by theintermediate diffusion model. It appeared that the rate ofuptake of the unionised form of these solutes wasdiminished due to the influence of interfacial or aqueousdiffusional barriers. Solute lipophilicity, degree ofionisation and diffusion coefficient appeared to beimportant factors determining the relative contribution ofthe interfacial barrier and the plastic matrix to theoverall diffusional resistance. Several approximations of the diffusion equations wereconsidered. These approximations suggested that the rateand extent of solute uptake by the plastics of deliverysystems at early times can be described by a singleparameter. In general these approximations yieldedparameter estimates consistent with those obtained bynonlinear regression using the full equations. A method ofdiscriminating between matrix-controlled and intermediatesorption kinetics, based on these approximations, is alsopresented.The kinetics of solute loss from solution to plastictubings during the course of an infusion was alsoinvestigated. The kinetics of loss could be interpreted interms of diffusion-controlled sorption of the unionisedsolute by the plastic. Equations are presented to describethe availability of diazepam, and possibly other solutes,during infusion.The interaction of chlormethiazole edisylate with theplastic infusion systems displayed some uniquecharacteristics, and these were further examined. It wasfound that, in some circumstances, chlormethiazoleedisylate was not only sorbed by the plastic, but alsopermeated to the external environment. Furthermore,plasticisation of the polyvinyl chloride by chlormethiazoleedisylate was observed. Some initial attempts at correlating the physicochemicalcharacteristics of a range of solutes with their plasticsorption behaviour are also presented.

Item Type:

Thesis
(PhD)

Keywords:

Drugs, Intravenous therapy, Plastics in medicine, Diffusion

Copyright Holders:

The Author

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